The present invention relates generally to solutions used in dialysis, i.e., in purification of blood by artificial means. More specifically, the present invention relates to the water-based chemical solutions used in the process of continuous ambulatory peritoneal dialysis and it further relates to antimicrobial compounds for use therein.
Dialysis is a medical therapy by which to achieve the blood-purifying function normally performed by the kidneys. Dialysis is most generally used in cases of chronic or acute renal insufficiency or failure associated with kidney disease or injury or during kidney operations or transplantations.
During dialysis, a patient""s blood, overloaded with catabolites (i.e., blood-borne metabolic waste), is brought into close contact with an artificial dialysis solution. (The terms xe2x80x9cdialysis solution,xe2x80x9d xe2x80x9cdialysis fluid,xe2x80x9d and xe2x80x9cdialysatexe2x80x9d are used interchangeably herein and have the same meaning.) The blood and the dialysis solution are separated from one another by a semipermeable membrane that can be either artificial or natural. The dialysis solution is formulated to be isotonic and in such a way that blood-borne catabolites cross the membrane from the blood to the dialysis solution by diffusion, thereby reducing the blood concentration of catabolites. The other critical function of dialysis is the removal of excess water from the body.
The efficiency of dialysis is directly related to a number of factors including at least volume of dialysis fluid, number of changes of dialysis solution and length of time between changes (or flow rate in a continuous system), surface area of membrane, pore size of the membrane, rates of diffusion of the toxins, and patient variables.
Hemodialysis is a specific type of dialysis in which the patient""s blood is withdrawn temporarily from the patient""s body and shunted through a machine containing the membrane and dialysis solution as well as pumps and temperature controls. Provision is made for blood to be drawn from the patient""s body and thence circulated through the machine, wherein it is exposed to the membrane surface. The catabolites migrate out across the membrane and water is removed by mechanical filtration. The treated blood is then returned to the patient""s body. Water is generally removed by hydraulic pressure across the membrane.
An alternative to hemodialysis is peritoneal dialysis (PD), which takes advantage of the living tissue membrane that lines the patient""s peritoneum, the peritoneum being the portion of the abdominal cavity located below the diaphragm and which contains the viscera. The principal difference between peritoneal dialysis and hemodialysis is substitution of the natural semipermeable capillary bed membranes that are abundant within the peritoneal cavity for the artificially provided semipermeable membranes of the hemodialysis machine.
In PD, the dialysis solution is introduced into the patient""s peritoneal cavity by way of an abdominal port or catheter. The dialysis solution is left inside the patient""s peritoneum for a period ranging from a few hours to overnight and then removed. During PD, that portion of the patient""s blood flowing most adjacent toe peritoneal membrane undergoes the blood-cleansing dialysis process. That is, the catabolites migrate across the patient""s peritoneal membrane from the blood to the dialysis solution. By flooding the interperitoneal extravascular space with isotonic dialysis solution, exchange of toxins from the blood occurs and dialysis is accomplished.
The concept of continuous ambulatory PD was introduced in the U.S. by Popovich and Moncrief in 1976. These authors revealed a method for continuous ambulatory peritoneal dialysis (CAPD), whereby the patient carries a bag made of a soft material, such as polyvinyl chloride, which contains the dialysis solution. The container of dialysis solution is connected through a tube from the soft bag into the peritoneal cavity of the patient.
In current day PD practice, a port or a catheter is placed within a patient""s abdomen so that it traverses the body""s outer surface. The port or catheter allows fresh dialysis solution to be introduced into the patient""s peritoneal cavity and drained from the peritoneal cavity once the solution becomes ineffective or spent, i.e., when the concentration of catabolites removed from the patient""s blood reaches a level in the dialysis solution that renders the solution inefficient at removing additional metabolites from the patient""s blood.
Typically, PD systems are configured such that there is a drain line and a fresh dialysis line attached to the end of the catheter protruding from the patient. Further, the connections between the fresh dialysis line and the catheter, the drain line and the catheter, and the fresh dialysis line and the drain line are all capable of being opened and closed as necessary. This allows for various techniques for filling and draining the peritoneal cavity with a dialysis solution.
PD has a distinct advantage over hemodialysis in that it allows the patient to receive treatment while performing normal daily activities without the sense of being incapacitated. Ambulatory continuous peritoneal dialysis normally takes place with approximately 4 exchanges per 24 hours.
With respect to water removal, in PD it is impossible to create a pressure gradient across the peritoneal membrane for the removal of water from the patient""s blood. Therefore, in PD, osmotic ultrafiltration is the mechanism whereby water is extracted from the blood to the dialysate. Water removal is achieved by providing a dialysis fluid with approximately normal blood electrolyte concentration and with an additional substance of preferably low diffusivity. Net water removal is achieved because water diffuses to the peritoneal cavity faster than the osmotic substance diffuses from the peritoneal cavity to the blood. The substance most commonly used is glucose, which diffuses into blood and achieves equilibrium within a few hours. The additional glucose load is normally acceptable because glucose is rapidly metabolized.
Osmotic ultrafiltration during PD is achieved by adding a large amount of, e.g., glucose to the dialysis solution as a way to maintain an initial high concentration of solute on the side of the membrane to which water is to flow from the blood to the dialysate. Glucose also prevents back flow of water from the dialysis solution into the patient""s blood. Alternative osmotic agents are amino acids, glycerol, or poorly absorbable carbohydrate polymers still under investigation.
A major likely complication of PD is peritonitis, i.e., infection of or within the peritoneal lining or peritoneal cavity respectively. The major route for infection is the catheter connection. For this reason many developments have been devoted to avoid contamination of the inner lumen of the fluid pathway during the connection process. UV-light and heat has been used to reduce bacterial contamination after connection. Conventional connectors have been replaced by special ones reducing the likelihood of contamination by skin contact. Also, methods have been developed reducing the likelihood of contamination, e.g., flushing fresh dialysate to drain initially before spent dialysate is removed.
Implanted ports and catheters through which the dialysis solution is introduced to and retrieved from the peritoneum also contribute to the incidence of peritonitis. Such port and catheters are disposed neither completely within the sterile realm of the body nor completely external to the body; that is, the ports and/or catheters used in dialysis traverse the body""s outer surface, thereby in effect exposing the sterile in-body realm to the pathogens of the outside world.
Additionally, the substances contained within dialysis solutions, especially glucose, dextrose, amino acids, and glycerol as mentioned above are conducive to the growth of bacteria. Therefore, even if the dialysis solution is sterile, the constituents of the solution can serve as an ideal culture medium for bacterial growth.
Moreover, the process of implantation of a peritoneal dialysis port or catheter provokes the body""s tissues most adjacent to the implanted device to form a tissue pocket or capsule around the implanted device. The capsule is the body""s way of isolating the foreign object from the body""s larger system. Typically the walls of such a tissue pocket or capsule have a thickness of a millimeter, more or less. Bacterial infection within the tissue pocket or capsule can take place during the implantation process. Bacteria residing within said capsule can later move to the peritoneal cavity thereby causing peritonitis.
After implantation of a dialysis port in a patient, infection can arise from skin bacteria being transported through the skin by needle penetration through the skin and into the port. Bacteria, having entered the space between the external surface of the device and the opposed tissue surface, can then attach to the port outer surface and grow into colonies in a layer or film form called biofilm. While initially localized within the pocket formed around a device, such a colony may not cause symptoms or manifest as an infection for a long time. However, bacteria from the biofilm colony may shed and cross the pocket membrane, whereby an infection will manifest itself systemically and/or within the peritoneum. Such an infection can become a local tissue infection indicated by local swelling, formation of pus, local inflammation and pain, and so on, and it can also lead to systemic blood infection. Such infections are serious, and if not treated often lead to morbidity and even death.
Notwithstanding improvements in the construction of subcutaneous ports, infection problems still impede their full usefulness in medical practice. Such infections are difficult to treat, often requiring the removal of the port or other implanted device, thereby subjecting the patient to additional trauma and leaving the patient without benefit of the device for the time it takes to clear the infection and replace the removed implant with another device. Moreover, the need to administer antibiotics frequently is expensive, and patients who suffer from repeated infections often breed strains of bacteria resistant to antibiotics. Such infections create a dilemma for patients who will lose access to life-sustaining renal replacement therapy.
It is therefore an object of the current invention to provide a method for disinfecting and for providing infection prophylaxis with respect to dialysis solutions. It is a further object of this invention to provide means of disinfecting or providing infection prophylaxis of the interior of implanted devices and catheters used in association with peritoneal dialysis. It is yet a further objective of this invention to provide a system for the use of non-antibiotic antimicrobial substances which do not cause the development of drug resistant strains of bacteria within peritoneal dialysis solutions.